Background: The removal of smear layer is necessary to achieve disinfection of the root canal system by deeper penetration of the root canal medicaments and irrigants. Various agents including organic acids, chelating agents, ultrasonics, and lasers have been used to remove the smear layer. Of these, the chelating agent ethylene diamine tetra-acetic acid (EDTA) in its different physical forms and formulations is most commonly used for smear layer removal; however, the search continues for newer and better agents. Objectives: The aim of this study was to systematically gather and evaluate the effectiveness of 17%EDTA for the removal of smear layer in root canals of human extracted teeth. Data Sources: A systematic search was conducted using MEDLINE, Google Scholar, Google and manual search using DPU College library resources upto 31st December 2015 to identify appropriate studies. All cross reference lists of the selected studies were also screened. Two reviewers assessed the eligibility of studies. Study eligibility criteria: In vitro and Comparative studies were selected;however, only articles where the effect of 17% EDTA on smear removal in root canals of freshly extracted human teeth were included.Review, case reports, abstracts, letters to editors, editorials were excluded. In vivo studies were excluded. Participants: Participants were comprised of freshly extracted human teeth. Interventions: Samples were subjected to 17% EDTA in all the studies. Results: 1817 articles from PubMed search was found relevant according to the inclusion criteria. An addition of 4 articles was included from other sources. A total of 31 records were screened according to title and selected. A final of 8 articles have been used for detailed evaluation in this systematic review after assessment of full text. 3 of these articles show similar efficacy of the respective irrigants used. In 5 studies 17% EDTA was effective in smear layer removal. Limitations: These studies do not give concrete conclusions due to an inadequate search of the literature because of less access to search forums, failure to evaluate the quality of studies, failure to exclude poorly designed studies, inappropriately combining heterogeneous studies,smaller sample sizes, availability of relevant articles in different languages other than English. Conclusion: 17% EDTA is effective for smear layer removal in root canals in human extracted teeth especially in cervical and middle third. But on increasing the duration of application it causes erosion of human dentin.